Stress is not a diagnosis, disease, or syndrome. It is a nonspecific set of emotions or physical symptoms that an individual experiences in response to forces, called stressors, which disrupt equilibrium or produce strain. [1,2]

In terms of health, stressors may be any life event or circumstance that exerts a physical, emotional, or cognitive demand on the individual.

Stress may or may not be associated with a disease or syndrome.

Not all stress is bad; it is generally believed that we need a certain amount of stress.

But when it occurs in quantities greater than the individual’s capacity to handle, pathological changes can occur.

Another suggested operational definition of stress is "anything that induces increased secretion of glucocorticoids", since that is what causes the responses to stress. [3]

Chronic stress has been defined as "a pathological state of prolonged threat to homeostasis by persistent or frequently repeated stressors … considered a significant contributing factor in the pathophysiology of a wide range of diseases and syndromes.” [4]

Stress depends not on what happens to an individual, but upon the way the individual reacts to what he or she experiences. [5]

As such, it should be more correctly described as ‘distress’, ‘the stressed state’, a ‘stress reaction’ or ‘strain’. [6]

Eustress is the good stress – a feeling of euphoria that accompanies the optimal level of stimulation.

2. STRESS: PREVALENCE AND TRENDS

The lifetime prevalence of major stressful life events is 100%, so associated stress-related symptoms may be considered a normal condition of human existence. [1]

Americans routinely experience unhealthy levels of stress.

8 in 10 U.S. adults (80%) say they have problems with stress in their lives. [7]

7 of 10 U.S. adults experience stress or anxiety daily, and most say it interferes at least moderately with their lives. [8,9]

About 1 in 3 report persistent stress or excessive anxiety daily. [8]

One-third report experiencing extreme levels of stress (32 percent) regularly, and nearly one in five (17 percent) report experiencing extreme stress 15 or more days per month. [9]

Nearly half (48%) report that that stress interferes with their activities every day (up from 39% in 2005). [8]

Women are much more affected than men (56% vs. 39%).

Nearly 3 out of 4 (72%) say it interferes at least moderately with their lives (up from 67% in 2005.

Overlap with anxiety:There is some overlap between an individual's perception of stress and anxiety disorders. Anxiety disorders are commonly seen in primary care and are frequently co-morbid conditions with major depression or other psychiatric disorders. [8a]

In primary care, 1 in 5 patients were found to have at least 1 anxiety disorder (1 in 12 with posttraumatic stress disorder, 1 in 13 with generalized anxiety disorder, 1 in 15 with panic disorder, and 1 in 16 with a social anxiety disorder. [8a]

Anxiety is often undetected and undertreated – 2 in 5 patients with anxiety disorders not treated.

Trends:For 6 in 10 (60%) life has become more stressful over the past year. [7]

Nearly half (48 percent) believe that their stress has increased over the past five years. [9]

Sources of Stress:

Work (74%) and money (73%) are on the rise as stressors (compared with 59% for each in 2006). [9]

Work is the top source of stress for adults - (39%), moreso for men (48%) than women (32%). [7]

Only 7% have sought help to manage their stress during the past year. [9]

3. STRESS: ETIOLOGY

The adaptive response to stress (the general adaptation syndrome, or fight or flight response) is well documented. It is our emergency response system that maintains our body's relatively steady internal state, or homeostasis, and prepares us to meet challenges. [11]

The delicate balance of biochemical and physiological function is constantly challenged by a wide variety of stressors, including illness, injury, and exposure to extreme temperatures; by psychological factors, such as depression and fear; and by sexual activity and some forms of novelty-seeking.

In response to stress, or even perceived stress, the body mobilizes an extensive array of physiological and behavioral changes in a process of continual adaptation, with the goal of maintaining homeostasis and coping with the stress.

It is a highly complex, integrated network involving the central nervous system, the adrenal system, and the cardiovascular system that allows the body to redirect oxygen and nutrients to the stressed body site, where they are needed most.

Psychosocial stress leads to a release of cortisol. [11a]

This response helps maintain physiological as well as psychological equilibrium under stress, but exaggerated or long standing elevations of cortisol have been shown to have negative effects on physical health and cognitive functioning.

Stress is usually thought of as harmful; but when the stress response is acute and transient, homeostasis returns, and no adverse effects result. [11,12]

But when the acute changes become chronic, the body does not return to homeostasis.

The chemical and hormonal changes do not fully return to the normal unstressed state and continue to exert effects on the physiological and psychological state.

Damage may occur, including immune system dysfunction, cell damage and accelerating a number of chronic disease processes.

Whether or not stress contributes to a disease or syndrome depends on the vulnerability of the individual; the intensity, duration, and meaning of the stress; and the nature and availability of modifying resources. [1]

Stress becomes distress if the individual’s capacity is overwhelmed OR if the individual even feels this to be the case.

Thus the key is the perception of a loss of control; in many people, stress is the result of an inaccurate perception of stress. [6]

There are clearly people who are more resistant to stress. Genes likely play a role. [13]

The diagnosis of Generalized Anxiety Disorder (GAD) increases vulnerability to stress. It appears to exist in about 10% of the population, but in 60% of those suffering from major depression.

Characteristics of people who are more resilient when it comes to handling stress include: [14]

Feeling in control rather than powerless,

The ability to see issues as a challenge rather than a threat.

4. STRESS: IMPACT ON HEALTH

The effect of stress on health becomes greater with increasing age due to the exaggerated response, the reduced capacity, and the extent of development of chronic disease. [15]

Aging is associated with an increase in the cortisol response to a challenge. This effect is almost three-fold stronger in women than men. [15]

An increased cortisol response to challenge is associated with a variety of age-related disorders such as Alzheimer's disease, depression, diabetes, metabolic syndrome, and hypertension.

Effect on health and well being:One in five adults aged 45 and older are suffering health problems due to financial stress, according to a survey by the American Association of Retired People (AARP). [16]

Both acute and chronic traumatic events (abuse, combat, injury, etc) in vulnerable individuals can result in an Acute Stress Reaction following the trauma which can lead to Post Traumatic Stress Disorder characterized by symptoms such as re-experiencing of the trauma (flashbacks and nightmares), avoidance behavior, hypervigilance and emotional numbing. [17a]

Prospective studies consistently indicate that hostility, depression, and anxiety are all related to increased risk of coronary heart disease and cardiovascular death.

A sense of hopelessness, in particular, appears to be strongly correlated with adverse cardiovascular outcomes

Although stressors trigger events, it is less clear that stress "causes" the events.

There is overwhelming evidence both for the deleterious effects of stress on the heart and for the fact that vulnerability and resilience factors play a role in amplifying or dampening those effects. [19,20]

The "Men Born in 1914” Study showed that men who chronically fail to find successful strategies to control their response in stressful situations are more vulnerable to the damaging effects of stress and at an increased risk of:

a future stroke in those with hypertension, [21]

death following a myocardial infarction, [22]

myocardial infarction and overall mortality in the presence of ventricular arrhythmias [23] or atherosclerosis. [24]

It has been long known that cardiac events can be triggered by external activities that trigger the sympathetic nervous system. [25]

The Multicenter Investigation of the Limitation on Infarct Size (MILIS) showed that half of acute MIs were associated with one or more triggers, most commonly emotional upset. [26]

A 40% increase in mortality rate, largely from cardiovascular causes, was found in widowers in the first 6 months following their spouse’s death. [25]

Immune System:The etiology of autoimmune diseases is multi-factorial, yet at least 50% of autoimmune disorders have been attributed to "unknown trigger factors". [27]

Physical and psychological stress has been implicated in the development of autoimmune disease, since numerous animal and human studies have demonstrated the effect of stressors on immune function.

Unfortunately, not only does stress cause disease, but the disease itself also causes significant stress in the patients, creating a vicious cycle.

It is presumed that stress-triggered neuroendocrine hormones lead to immune dysregulation, which ultimately results in autoimmune disease by altering or amplifying cytokine production.

The treatment of autoimmune disease should thus include stress management and behavioral intervention to prevent stress-related immune imbalance.

Weight Gain:A high level of stress is a predictor of major weight gain; and this effect was consistent in some groups even over 15 years. Low levels of life satisfaction and high scores for neuroticism, were predictors of weight gain in older women. [28]

5. STRESS: RELATION TO ALCOHOL

Drinking alcohol induces the stress response, that is, some of the body's responses to alcohol are similar to its responses to other stressors. [29]

Yet, individuals often drink to relieve stress.

Stress responses are not exclusively unpleasant; the arousal associated with stress itself may be rewarding.

The initial response to alcohol is variable. Some studies have reported that acute exposure to low doses of alcohol actually reduces the response to a stressor while, in others, it induces the stress response. [30]

But, one thing is certain – intoxication causes a stress response in the body.

Stress does not lead individuals to drink more often, but rather to drink larger quantities when they do consume alcohol. [31]

Data from the 2001-2002 National Epidemiologic Survey on Alcohol and Related Conditions (NESARC) showed a consistent positive relationship between number of past-year stressors experienced and all measures of heavy drinking.

Frequency of heavy (5+ drinks for men; 4+ drinks for women) drinking increased by 24% with each additional stressor reported by men and by 13% with each additional stressor reported by women.

In contrast, the frequency of moderate drinking decreased as stress levels increased.

Job-related and legal stressors were more strongly associated with alcohol consumption than were social and health-related stressors.

Men showed a stronger association than women between the number of stressors and consumption of alcohol. Having an income below the poverty level intensified the effects of job-related stress.

Treatment and brief interventions aimed at problem drinkers might benefit from addressing the issue of tension alleviation and the development of alternative coping mechanisms.

Individuals experiencing a higher frequency and perceived severity of job stressors have been shown to be more likely to drink and to be heavy drinkers. [32]

A direct relation has been observed between work-related stressors and elevated alcohol consumption and problem drinking. [33]

People under stressful conditions are more likely to either abstain or drink heavily rather than to drink lightly or moderately. [34]

Some life events (being a victim of a crime, decrease in financial position, divorce) are positively associated with heavy drinking in men.

Chronic stressors, such as marital problems and job problems, are related to heavy drinking in both men and women.

Individuals exposed to stress are more likely to abuse alcohol and other drugs or undergo relapse. [35-37]

The Health and Retirement Study showed that changes in drinking behavior were related to several life events occurring over a 6-year period. [38]

A new health problem was associated with decreased drinking levels.

Retirement was associated with increased drinking.

Getting married or divorced was associated with both increases and decreases in drinking.

A history of problem drinking influenced the association between certain life events (e.g., divorce and retirement) and changes in drinking.

This is especially noteworthy in view of the lower tolerance to alcohol that comes with increasing age.

Supportive resources of family, friends, and church appear to have stress-buffering effects that reduce excessive-drinking in response to life crisis.

Whether an individual will drink in response to stress appears to depend on many factors, including genes, usual drinking behavior, expectations that alcohol will help reduce stress, intensity and type of stressors, sense of control over stressors, and availability of social support. [40-43]

6. STRESS: CURRENT PRACTICE PATTERNS

There is very little documentation of the use of stress management counseling in primary care.

Even studies that specifically address physician counseling for lifestyle behaviors do not include stress management – typically include only inactivity, poor diet, excessive alcohol consumption, and smoking. [45]

One survey of primary care providers that did address stress management found that: [46]

42% received no instruction regarding stress and health outcomes during their medical/professional education.

It would be safe to assume that use, self efficacy and training would be even worse for stress management because there is less evidence of effective assessment and intervention.

7. STRESS: MANAGING STRESS

Thus there are two factors to consider in any stressful situation: [6]

The external factor, or stressor, that causes the stress response in the individual, and

The internal factors, the reaction, within the individual that lead to the stress response.

A feeling of loss of control, whether real or perceived, differentiates stress from the distress that can lead to anxiety and depression. [6]

Restoring a feeling of perceived control is a primary goal of stress reduction.

This can be achieved by:

Removing the stressor (or the individual from the stressor),

Reducing the potency of the impact of the stressor on the individual, or

Changing the individual’s response to the stressor.

The strategy used is the "escape” (i.e., from the stressor)

How an individual interprets and responds to the environment determines responses to stress, influences health behaviors, contributes to the neuroendocrine and immune response, and may ultimately affect health outcomes. [44]

Health psychology interventions are designed to modulate the stress response and improve health behaviors by teaching individuals more adaptive methods of interpreting life challenges and more effective coping responses.

Identify the stressors or triggers; they are often multi-factorial.

Psychosocial, workplace, or socioeconomic issues can be explored with the patient to facilitate early identification of precipitating factors and appropriate interventions that may prevent delayed recovery or relapse.

An open, honest discussion of the underlying factors often results in an increase in the patient's insight and coping skills, which itself helps alleviate many stress-related symptoms.

Encourage patients to enhance their individual coping skills and to decrease or discontinue maladaptive coping mechanisms such as excessive use of alcohol, tobacco, or other drugs, or excessive food intake. [1]

Referring to mental health professionalsPatients with high levels of stress who have an anxiety disorder are probably better served by seeing a mental health professional than having their primary care physician practicing in an area where they do not have training/expertise.

The referral may be to a clinical psychologist, not just a psychiatrist.

Referral is also appropriate for other patients whose stress issues may demand more intensive counseling. Identifying stressors and counseling to enhance coping skills are beyond the scope of many primary care practices.

This work consumes time PCPs do not have and calls for skills they also do not have.

The best strategy is often to use a mental health professional, again either a clinical psychologist or psychiatrist.

Escaping stressors – managing the stress responseThere are many options and strategies to use to ‘escape’ the stressor. [50]

Stress reduction and resistance can be enhanced by regular exercise, a diet rich in a variety of whole grains, vegetables and fruits, and by avoiding excessive alcohol, caffeine and tobacco.

Exercise: Exercise is important for two important reasons: [50]

It serves as an effective distraction from stressful situations, and

It helps to blunt the harmful effects of stress, especially regarding the cardiovascular system

Many studies have demonstrated the positive psychological effects of regular aerobic exercise, including reduced perceived stress, reduced anxiety or depressive symptoms, and an increase in self-esteem.

The acute effect of exercise on stress and anxiety is well established; this supports the importance of regular exercise to manage the daily stress response. [51]

This is also why activity level has been shown to be more important for stress-buffering than fitness level; the positive effect on stress hormones is achieved with each session of exercise. [52]

Exercise induces a down-regulation of certain central serotonergic receptors, which play an important role in the pathogenesis of both anxiety and depression. [53]

It also prevents the stress-induced suppression of the immune system, and the balancing of brain chemicals. [54]

Advising patients regarding exercise for stress management: [50]

Find an activity that is convenient – that’s why walking is usually best to depend on.

Find another activity that they enjoy, and that may be a little more challenging.

Start small – even a 10-minute brisk walk is helpful.

Be regular -- better to do a little every day than more on the weekend only.

Plan activities and set some goals, with a reward for when they are achieved.

Try a yoga or Tai Chi class – both have been shown to be great for stress reduction.

Cognitive Behavioral Therapies:Cognitive behavioral therapies (CBT) are among the most effective ways of reducing stress. [50]

A systematic review of the efficacy of CBT for a variety of anxiety disorders showed that it is an effective treatment for anxiety and acute stress disorders. [55]

Cognitive-behavioral stress management training has been shown to significantly reduce the cortisol response to an acute stressor in healthy subjects. [56,57]

A typical CBT approach includes: [50]

Identifying the sources of stress,

Assessing sources of stress – are they reasonable, how they fit personal goals, how much control the patient has over them.

However, practitioners, even psychiatrists, typically receive little format training in CBT, and it is a therapy that requires training in the specific issue addressed (e.g., depression, stress) to be effective.

The general principles are useful, but if a patient requires formal CBT, a referral to a trained practitioner should be made.

Meditation: A review of evidence regarding approaches for stress reduction showed that meditation was most effective -- associated with significant reductions in BP, as well as other CVD risk factors and clinical outcomes. [58]

Low intake of alcohol:Several experimental studies have found that low to moderate alcohol consumption can reduce the immediate effects of stress in some people. [59]

However, alcohol used to reduce stress may not be a good idea for all people due to the possibility of it leading to misuse and addiction.

Alcohol intake has been shown to have a U-shaped relationship with psychological distress.

At moderate levels, work stress was reduced, but as alcohol intake increased, the effect of work strains was intensified. The results give some support to the positive effect of moderate alcohol consumption on stress reduction and mental health. [60]

Medications:Medications have a limited role. [1]

Anti-anxiety agents may be used for short periods of time (i.e., when overwhelming anxiety limits the patient's ability to work or effectively perform the activities of daily living), but continued use is not advised due to the possibility of misuse and risk of addiction.

Antidepressant medications may be prescribed if major depression is involved.

8. STRESS: GUIDELINES

GUIDELINE: ACOEM -- Stress-related conditions [1]

Basic Principles and Major Recommendations:

Stress is a nonspecific set of emotions or physical symptoms that may or may not be associated with a disease or syndrome. Whether or not it contributes to a disease or syndrome depends on the vulnerability of the individual; the intensity, duration, and meaning of the stress and the nature and availability of modifying resources.

Jennison, K.M. The impact of stressful life events and social support on drinking among older adults: A general population survey. International Journal of Aging and Human Development 35(2):99-123, 1992.

Leading health-related guidelines recommend "safe” levels of alcohol consumption for adults as no more than 2 drinks per day for men and 1 drink per day for non-pregnant women. [1-4] The U.S. Preventive Services Task Force [5,6] defines unsafe drinking as:

"Risky” or "hazardous” drinking -- more than 14 drinks per week or more than 4 drinks per occasion for men or more than 7 drinks per week or more than 3 drinks per occasion for women.

"Harmful” drinking includes those who are currently experiencing physical, social, or psychological harm from alcohol use but do not meet criteria for dependence.

Alcohol "misuse” includes "risky/hazardous” and "harmful” drinking that places individuals at risk for future problems.

Alcohol "dependence” includes drinkers who continue to use alcohol despite significant negative physical, psychological, and social consequences. [7]

They generally meet criteria for abuse or dependence as outlined in the Diagnostic and Statistical Manual of Mental Disorders, fourth edition, and are candidates for specialty addiction treatment. [8]

Overall, 1 in 5 adults >18 years had five or more alcoholic drinks in a single day at least once in the preceding year. [13]

For both men and women, the percentage decreased with age. Men were substantially more likely than women to have had five or more drinks in 1 day at least once in the preceding year.

The percentage of whites who reported five or more alcoholic drinks in 1 day at least once during the preceding year, at 24.3%, was more than twice the percentage of blacks (12.0%) and significantly higher than Hispanics or Latinos (16.5%)

Another 1 in 10 adults exceeded the weekly (but not the daily) limits. [14]

Percentage of adults who reported any current drinking, BRFSS, 2006: [10]

Overall:

55%

Men:

61%

Women:

48%

Percentage of adults who reported heavy drinking, BRFSS, 2006: [15](an average of > 2 drinks per day for men, or > 1 drink per day for women during the past month)

Overall:

5%

Men:

6%

Women:

4%

Percentage of adults who reported binge drinking, BRFSS, 2006: [16](5 or more drinks on at least one occasion during the past month)

Overall:

16%

Men:

21%

Women:

10%

A Gallup Poll showed that 62% of adults drink alcohol to some degree (2008). [12] Percent distribution of current drinking status, drinking levels, and heavy drinking days by sex for persons 18 years of age and older: United Status, National Health Information Survey (NHIS, 2006). [11]

Abstainers:

Overall: 25%

(Men: 18%, Women: 32%)

Former Drinker:

Overall: 14%

(Men: 15%, Women: 14%)

Current Drinker:

Overall: 61%

(Men: 68%, Women: 54.5%)

Light Drinker:

Overall: 41%

(Men: 40%, Women: 43%)

Moderate Drinker:

Overall: 14.5%

(Men: 22%, Women: 7.5%)

Heavy Drinker:

Overall: 5%

(Men: 5.5%, Women: 4.6%)

Percent reporting alcohol use in the past year by age group and demographic characteristics: NSDUH (NHSDA), 1994–2002. [17]

35+:

66%

18-34 yrs:

78%

The BRFSS of adults aged 18+ showed that between 1993 and 2001, the total number of binge-drinking episodes increased from approximately 1.2 billion to 1.5 billion; episodes per person per year increased by 17% (from 6.3 to 7.4). [18]

Between 1995 and 2001, binge-drinking episodes per person per year increased by 35%.

The National Institute on Alcohol Abuse and Alcoholism (NIAAA) and others encourage physicians to identify patients with alcohol-related risks or problems and to provide office-based brief interventions or referrals as needed. [20,21]

In everyday practice, screening procedures using a standardized instrument (such as the AUDIT-C) are necessary to identify the range of alcohol users in order to offer appropriate treatment. [22,23,23a]

Early identification of alcohol-related problems is important because these problems are prevalent, pose serious health risks to patients and their families, and are amenable to intervention. [24]

Early intervention can lower morbidity and prevent progressive damage to family and social relationships.

Primary care physicians are encouraged by the NIAAA to screen patients not only for alcohol abuse and dependence, but also for alcohol consumption that would place them at risk for current or future adverse health events. [1,6]

The rationale is that primary care physicians can play an instrumental role in recognizing alcohol problems, initiating therapy, providing advice for further treatment options, monitoring response to therapy, and promoting relapse prevention. [25,26]

Primary care physicians provide routine care for a large number of patients with alcohol problems; prevalence rates range from 2% to 29%, depending on the type of disorder, in ambulatory patients. [27-29]

Prevalence of alcohol misuse is generally higher in males and younger persons of all races and ethnicities. [30]

About 8% to 18% of patients screen "positive," and would be candidates for brief interventions. [32-36]

About half of these would be eligible for primary care intervention after completing an assessment. [37]

15. ALCOHOL: IMPACT ON HEALTH

A state of the science report from the NIAAA [38] on the effects of alcohol on health outcomes concludes that:

Current scientific evidence continues to show that moderate levels of alcohol consumption do not increase risk for heart failure/ myocardial infarction or ischemic stroke, and in fact provide some protective effects along a J-shaped curve.

The lowest total all-cause mortality occurs at the level of 1 - 2 drinks per day.

There is some evidence for reduced risk of diabetes and metabolic syndrome.

Protective levels of consumption cannot be generalized across the population, but instead should be determined for each patient individually.

The potential for moderate alcohol consumption to reduce risk for one disease may be outweighed by its potential to increase risk for another disease, depending on family history, medical history, genetic makeup, and lifestyle.

The risk for breast cancer increases with any alcohol consumption.

Appears to be a 10% increase in risk for women averaging 1 drink per day, higher with a family history of breast cancer or on hormone replacement therapy.

There is no question that excessive consumption during pregnancy can produce a range of behavioral and psychosocial problems, malformations, and mental retardation in the offspring.

The current scientific knowledge on the risks and benefits related to alcohol consumption suggests that a moderate consumption of 2 drinks a day for men and 1 for women is unlikely to increase health risks.

BUT as consumption rises above this level, risks for some conditions and diseases (including alcohol misuse/abuse/dependence) increases in direct relation to the increase in consumption.

Excessive alcohol can be addictive, and high intake can be associated with serious adverse health and social consequences, including hypertriglyceridemia, hypertension, liver damage, physical abuse, vehicular and work accidents, and increased risk of breast cancer. [4]

MortalityMen averaging at least 4 drinks per day and women averaging 2 or more drinks per day have been shown to have significantly increased mortality relative to nondrinkers. [39]

Alcohol has an acute and profound effect on fibrinolysis that may be relevant to the pathogenesis of CVD.

Drinking a large amount of alcohol results in an acute inhibition of fibrinolysis; may predispose to accelerated atherosclerosis and set the stage for thrombotic coronary events, explaining the higher cardiovascular mortality risk in binge drinkers.

Binge drinking is associated with an increased risk of cardiovascular events. [41]

Those events often happen within hours after alcohol is consumed. Apart from arrhythmias and changes in blood pressure, these events may be caused by an acute (i.e., occurring within a 24-h period) shift of the hemostatic balance in a thrombogenic direction.

The Prospective Epidemiological Study of Myocardial Infarction (PRIME) showed that a binge-drinking pattern led to fluctuations in blood pressure levels, whereas no such fluctuations in blood pressure levels are found for regular consumption. [42]

It increased the risk of hypertension in men (HR = 1.57) but not in women.

Psychiatric problemsThe NESARC dataset, the largest and most ambitious co-morbidity study ever conducted, demonstrated the strong links between alcohol use disorders (AUDs) and a range of psychiatric problems—from pathological gambling and nicotine dependence to anxiety disorders and major depression. [44]

Taken together, the findings from these papers highlight the high prevalence and diversity of co-morbidity and underscore the need for clinicians to diagnose and treat co-morbid conditions as well as AUDs.

Kidney diseaseClinical and experimental studies have demonstrated that the habitual consumption of large amounts of ethanol has deleterious effects on the kidney. [45]

A variety of tubular defects have been described in patients with chronic alcoholism.

These renal abnormalities are often reversible, disappearing with abstinence.

Liver disease Alcohol exerts some harmful effects through its breakdown (i.e., metabolism) and the resulting toxic compounds, particularly in the liver, where most alcohol metabolism occurs.

The incidence of liver disease has been strongly increased among high risk drinkers (OR=2.78-4.76). [46]

Injury rates are higher for infrequent binge drinkers, even when average intake is not excessive. [48]

16. ALCOHOL: RELATION TO STRESS

The effect of alcohol on the stress response is a function of amount.

The body responds to stress through a hormone system called the hypothalamic-pituitary-adrenal (HPA) axis. Stimulation of this system results in the secretion of stress hormones (i.e., glucocorticoids).

Intoxication results in greater activation of the HPA axis and results in elevated glucocorticoid levels. [49]

This supports the greater harm associated with larger amounts of alcohol in a single occasion.

In addition, in heavy drinkers, the stress response is not turned off as effectively as in light drinker and non-drinkers. [50]

Data from the 2002-2004 phase of the Whitehall II study of British civil servants showed that, in men, there was a 3% increase in cortisol per unit of alcohol consumed each week.

The slope of the cortisol decline during the day in heavy drinkers was reduced, indicating less control of the HPA axis in heavy drinkers, that is, the stress response was not turned off as effectively.

Data from the BRFSS shows that frequent binge drinking is associated with significantly worse health-related quality of life (HRQOL) and mental distress, including stress, depression, and emotional problems. [51]

Other studies have reported that individuals exposed to stress are more likely to abuse alcohol and other drugs or undergo relapse. [52-54]

17. ALCOHOL: RELATION TO DEPRESSION

The 2006 BRFSS found that those who drank alcohol "heavily” (> 2 drinks per day for men, or > 1 drink per day for women during the past month) were significantly more likely than those who did not to have current depressive symptoms. [55]

The prevalence of 12-month mood and anxiety disorders in the US population was 9% and 11%, respectively, while the rate of substance use disorders was 9%. [56]

Associations between most substance use disorders and independent mood and anxiety disorders were overwhelmingly positive and significant.

NIAAA data show that the prevalence of depression increases with alcohol consumption, from 1 in 17 of moderate drinkers to 1 in 11 heavy drinkers to 1 in 5 with alcohol dependence.

For most race/ethnic subgroups, alcohol dependence, but not abuse, is significantly associated with mood disorders. [57]

Prior alcohol dependence increases the risk of current major depressive disorder by more than 4-fold. [58]

Depression is primarily related to drinking larger quantities per occasion (binge drinking), less related to volume, and unrelated to drinking frequency, and this effect is stronger for women than for men. [59,60]

The overall relationship between depression and alcohol consumption is stronger for women than for men, but only for major depression and not when measured as recent depressed affect.

They also experienced more life stressors and had lower mental/psychological quality-of-life scores.

Blacks less likely to be treated for coexisting depressionThe 2001-2002 National Epidemiologic Survey on Alcohol and Related Conditions (NESARC) showed that, compared to whites, blacks with co-occurring mood or anxiety and substance use disorders were significantly less likely to receive services for mood or anxiety disorders, equally likely to receive services for alcohol use disorders, and more likely to receive some types of services for drug use disorders. [62]

18. ALCOHOL: CURRENT PRACTICE PATTERNS

Although health care settings offer an ideal opportunity for identifying people who are currently experiencing or are at risk for problems with alcohol, clinicians screen fewer than half of their patients for alcohol use disorders. [63,64]

Data from observational field notes on actual health care maintenance visits, medical record reviews, and in-depth interviews for 95 visits of adult females to 47 different clinicians at 18 Midwestern urban, suburban, and rural family practices showed that alcohol use screening occurred in less than one-third of visits. [65]

Despite evidence that brief interventions are useful in the primary care setting, these short counseling sessions are not routine practice.

One survey of primary care physicians found that most (88%) reported asking their patients about alcohol use. [66]

Nearly half inquired about maximum amounts on an occasion, but just over 1 in 10 use formal alcohol screening tools.

A survey of primary care patients revealed that over half said their primary care physician did nothing about their substance abuse; 43% said their physician never diagnosed their problem. [68]

Factors contributing to under-diagnosis include depression, dementia, physical changes associated with age, life events, late onset of alcoholism and lack of screening. [69]

One analysis found that more than 30% of depressed women and men visiting primary care doctors had drug or alcohol problems. Yet only 8%, mostly men, had been counseled about drug or alcohol use during their most recent primary care visit.

Men were three times as likely to have been counseled as women about these problems (15.6 vs. 4.5 percent). [70]

Some providers report finding it difficult to confront patients who drink excessively. [71]

Treatment is also inadequateFewer than 1 in 4 of those with alcohol dependence are ever treated, slightly less than the rate found 10 years earlier. [72]

19. ALCOHOL: GUIDELINES

The U.S. Preventive Services Task Force (USPSTF)RecommendationsThe USPSTF recommends that primary care physicians screen patients for problem drinking and intervene to reduce these patients' intake of alcohol. There is good evidence of benefit in this approach and little evidence of harm. [5]

Patients with past alcohol problems, young adults, and other high-risk groups (e.g., smokers) may benefit from more frequent screening.

The method of administering the screening is important too.

Many clinics have a nurse administer the screen. This may be cost effective, but it may adversely affect the yield because some patients fear the stigma of admitting to alcohol problems to a nurse.

In one study, when the AUDIT-C was administered face-to-face (usually by a nurse), the yield of alcohol misuse was about 23%, whereas when the AUDIT-C was administered to the same individuals via a mailed anonymous questionnaire, the yield was about 35%. [80a]

Positive screenings for abuse/dependence need to be followed by a diagnostic evaluation using DSM-IV criteria for abuse/dependence. [80b]

If the patient meets these criteria, the primary care provider should focus on facilitating the patient to at least consider specialized addiction assessment and treatment.

Positive AUDIT scores were not followed up with a diagnostic evaluation unless these were specifically required.

Criteria for Alcohol AbuseA diagnosis of alcohol abuse requires that the patient meet one or more of the following criteria, occurring in the same 12-month period, and not meet the criteria for alcohol dependence. [80c]

A single question to use during a clinical interview (Step 1 below) OR

A written self-report instrument (the AUDIT, see Resources).

The single interview question can be used at any time, either in conjunction with the AUDIT or alone. Some practices prefer to have patients fill out the AUDIT before they see the clinician; takes less than 5 minutes and can be copied or incorporated into a health history.

Clinical indications for screening:

As part of a routine examination

Before prescribing a medication that interacts with alcohol

When seeing patients who

are pregnant or trying to conceive

are likely to drink heavily, such as smokers, adolescents, and young adults

have health problems that might be alcohol induced, such as:

cardiac arrhythmia

dyspepsia

liver disease

depression or anxiety

insomnia

trauma

have a chronic illness that isn't responding to treatment as expected, such as:

chronic pain

diabetes

gastrointestinal disorders

depression

heart disease

hypertension

Guidelines for a brief intervention:

Step 1: Ask about alcohol use (or review AUDIT form)

Do you sometimes drink beer, wine, or other alcoholic beverages?

If YES, How many times in the past year have you had . . . 5 or more drinks in a day? (for men) OR 4 or more drinks in a day? (for women)

If 1 or more go to Step 2

If 0 counsel on daily and weekly alcohol limits for health; tailor to individual risk factors

INTERVENTIONS Brief interventions—or short, one-on-one counseling sessions—are ideally suited for people who drink in ways that are harmful or abusive, but do not have severe drinking problems. [91]

Unlike traditional alcoholism treatment that lasts many weeks or months, brief interventions can be given in minutes, and require minimal follow-up.

They typically consist of 1-4 short counseling sessions with a trained interventionist (e.g., physician, psychologist, social worker).

The goal is generally to reduce alcohol consumption to sensible levels and eliminate harmful drinking patterns (such as binge drinking).

The most basic level of brief intervention consists of a simple statement or two. [91]

The clinician states that he or she is concerned about the patient’s drinking, that it exceeds recommended limits and could lead to alcohol-related problems, and the clinician advises the patient to cut down or stop drinking.

It is important to clearly distinguish between alcohol misusers and those with diagnosable alcohol disorders.

Reducing alcohol consumption to "sensible levels” is not indicated for those with alcohol disorders.

Evidence clearly supports abstinence as the appropriate goal for these individuals.

Trials of harm reduction in the presence of abuse/dependence disorders has been associated with significant adverse outcomes.

Advantages of brief interventions Many people avoid lengthy treatment for alcohol problems because they perceive it to be embarrassing, stigmatizing, and inconvenient, taking too much time away from work or family responsibilities. They are more likely to accept a brief intervention. [92]

Brief interventions provide a simple approach in a comfortable and familiar setting,

They are easily incorporated into a family practice, delivered by familiar people in a familiar setting.

They are a lower cost alternative to formal, specialist-led, alcoholism treatment.

Supplemental handouts may be provided to reinforce the strategies offered during the session.

Clinicians can follow up at a later date, either in person, through the mail, or by phone to provide additional assessment and further motivate the patient to achieve the goals set during the initial meeting.

If the brief intervention does not work, clinicians can always recommend more intensive treatment.

Motivational interviewing can help with reluctant patientsBrief interventions may include motivational interviewing to persuade people who are resistant to moderating their alcohol intake or who do not believe they are drinking in a harmful or hazardous way. [93]

It encourages patients to decide to change for themselves by using empathy and warmth rather than confrontation. Clinicians assist patients by helping them set specific goals and build skills for modifying their drinking behavior.

Motivational interviewing generally requires some training. If practitioners are not able/willing to get this training it might be best to develop an affiliation with providers who are trained.

Brief interventions are effective

A systematic review of 34 studies found that people who received brief interventions when they were being treated for other conditions consistently showed greater reductions in alcohol use than comparable groups who did not receive an intervention. [94]

The U.S. Preventive Services Task Force in 2004 found good evidence that brief behavioral counseling interventions with follow-up produce small to moderate reductions in alcohol consumption that are sustained over 6- to 12-month periods or longer. [5,95]

The intervention led to 10% to 19% more participants than controls achieving safe or recommended drinking levels.

They also reduced weekly drinking by 2.9 to 8.7 drinks per week more than in controls (13% to 34% net reductions), but had inconsistent effects on binge drinking.

All interventions that showed statistically significant improvements in alcohol outcomes of any intensity included at least 2 of 3 key elements: [98]

feedback

advice

goal-setting

Since most effective interventions were multi-contact ones, they also provided further assistance and follow-up. A few also reported tailoring intervention elements to each participant. [99-101] Very brief (5 min) or brief single-contact interventions were shown to be not effective in reducing risky/harmful alcohol use. [102]

Use a Chronic Care ModelThe Chronic Care Model (CCM), originally designed to improve care for patients with chronic conditions, such as diabetes and hypertension, is also applicable to a broad range of individuals with alcohol use disorders. [95]

The CCM is a heuristic model that offers an approach to increase the ability of PCPs to identify, treat and effectively manage AUDs.

While simple advice or very brief interventions may be more easily incorporated into routine care, the effectiveness of risky/harmful alcohol use interventions depends on multiple contacts over time.

Studies consistently show that additional staff and systems support are required to optimize screening and assessment services, and intervention support.

Set up the practice to simplify the process: [110]

Decide the type of screening to use (single question or survey form – AUDIT)

Decide who will conduct the screening (you, other clinical personnel, the receptionist who hands out the survey, or mailed out (this is a key issue that affects the honesty of the responses; may need to be adjusted with time)

Advanced in delivering brief interventions Many of the obstacles involved in administering brief interventions—such as finding the time to administer them, obtaining the necessary training, and the cost of the interventions—can be reduced by developing technology.

Patients can use computer programs in the waiting room or at home, or access interventions over the Internet, which offers privacy and the ability to complete the program at any time of day. [111,112]

Another option is "video doctor technology,” in which an actor–doctor asks health questions in an interactive computer program. Pilot results of this program indicate that users are more comfortable consulting a doctor in person, but view the "virtual” doctor intervention positively. [113]

U.S. Department of Agriculture and U.S. Department of Health and Human Services. Dietary guidelinesfor Americans. Washington, DC: Department of Agriculture, 1990.

Dietary Guidelines Advisory Committee. Report of the Dietary Guidelines Advisory Committee on thedietary guidelines for Americans, 1995, to the Secretary of Health and Human Services and the Secretaryof Agriculture. Washington, DC: U.S. Department of Agriculture, 1995.

U.S. Department of Health& Human Services. National Institutes of Health National Institute on Alcohol Abuse and Alcoholism. National Epidemiologic Survey on Alcohol and Related Conditions, Number 70 October 2006. http://pubs.niaaa.nih.gov/publications/AA70/AA70.pdf

Depression is a serious medical condition that involves the body, mood, and thoughts. [1]

It is characterized by changes in mood, self-attitude, cognitive functioning, sleep, appetite, and energy level.

It affects the way we eat and sleep, the way we feel about ourselves, the way we think about things.

It is not the same as a passing blue mood, a sign of personal weakness or a condition that can be willed or wished away.

People with a depressive illness cannot merely "pull themselves together" and get better.

Without treatment, symptoms can last for weeks, months, or years.

Appropriate treatment, however, can help most people who have depression.

Major depression is a clinical syndrome of at least five symptoms that cluster together, last for at least 2 weeks, and cause impairment in functioning; symptoms range from mild and chronic to severe and more acute (DSM-IV). [2]

Mood symptoms include depressed, sad or irritable mood, loss of interest in usual activities, inability to experience pleasure, feelings of guilt or worthlessness, and thoughts of death or suicide.

Cognitive symptoms include inability to concentrate and difficulty making decisions.

Physical symptoms include fatigue, lack of energy, feeling either restless or slowed down, and changes in sleep, appetite, and activity levels.

Depressive symptoms may occur in a variety of conditions (bipolar disorder, schizoaffective disorder, dysthymia, etc.) which have very different implications for treatment.

The information presented here applies to major depressive disorder (MDD), as well as subthreshold depressive symptoms (i.e., not meeting full diagnostic criteria for MDD).

A clear diagnosis needs to be made to screen out patients for whom the standard treatment of MDD might not be appropriate (e.g. bipolar depression) to avoid possible adverse results.

It should be noted that a text revision of 1994 DSM-IV, called DSM-IV-TR,was published in July 2000 (next revision is 2012). For a summary of practice relevant changes, go to:

Depression is becoming widely characterized as a chronic disorder, like diabetes, hypertension, or asthma, based partly on its high recurrence rate. Approximately half of those diagnosed with depression experience a recurrence within 2 years, and more than 80% within 5 to 7 years. [3-5]

25. DEPRESSION: PREVALENCE AND TRENDS

Depression is one of the most prevalent and debilitating mental health conditions, affecting 17.6 million Americans of all ages each year. [6]

Many more people live with some undiagnosed depressive symptoms that reduce their ability to lead full and productive lives.

It can be an episodic condition. Some people have an episode, get well, and may or may not have another episode later in their life.

In 2005-2006, during any 2-week period, more than 1 in 20 Americans 12 years of age and older (5.4%) had depression. [7]

Rates were higher in 40-59 year olds, women, non-Hispanic black persons, and poor persons than in other demographic groups.

Women vs men: 7% vs 4%

Age 40-59 vs other ages: 7% vs 4%

Black vs White: 8% vs 5%

Below poverty level vs At or above poverty level: 13% vs 4%

Age 40-59 AND below poverty level vs Age 40-59 AND at or above poverty level: 22% vs 6%

The 2006 Behavioral Risk Factor Surveillance Survey showed that the overall prevalence of current depressive symptoms was 8.7%. [8]

Cardiovascular disease, diabetes, asthma, smoking, and obesity were all significantly associated with current depressive symptoms, as well as a lifetime diagnosis of depression.

Physically inactive adults were significantly more likely than those who were physically active to have current depressive symptoms or a lifetime diagnosis of depression.

Those who drank heavily were significantly more likely than those who did not to have current depressive symptoms or a lifetime diagnosis of anxiety.

The prevalence of a lifetime diagnosis of depression has been shown to be 13% to 15%. [8,9]

The highest risk of major depression currently occurs in baby boomers, a shift from the younger adult population shown to be at highest risk during the 1980s and 1990s. [11]

This marks an important transformation in the distribution of major depressive disorder (MDD) in the general population and specific risk for those aged 45 to 64 years.

Depression in the elderly is also a common clinical problem seen in the primary care setting with prevalence estimates of 6-9%. [11a]

Similar to the younger population, depression in the elderly is commonly unrecognized or under-recognized, and treatment is either absent or inadequate.

26. DEPRESSION: ETIOLOGY

The development of depression seems to be related to a chemical imbalance in the brain that involves the brain's neurotransmitters. [12]

This imbalance makes it hard for the cells to communicate with one another; a reduction in the activity of serotonin, one of these neurotransmitters, appears to be an important factor in the development and severity of depression.

A genetic component has also been identified.

A number of factors are associated with an increase in the incidence of depression.

Stressful events, such as the death of a loved one, a divorce or loss of a job

Depression may also develop for no apparent reason in some people who have a genetic predisposition toward a depressive mood state.

Depression is not caused by personal weakness, laziness or lack of willpower. [12]

Relation to lifestyle habits:Depression can lead to worsening health habits, including: [13]

an increase in cigarette consumption

excessive alcohol use

a decrease in physical activity

Relation to Alcohol:Excessive alcohol use, as well as smoking and drug use, is more common with depression. [11,15]

Among persons with current MDD, about 1 in 7 also have an alcohol use disorder (1 in 20 have a drug use disorder, and 1 in 4 have nicotine dependence).

Among persons with lifetime MDD, 2 in 5 had experienced an alcohol use disorder, (nearly 1 in 5 a drug use disorder, and 1 in 3 nicotine dependence).

The NESARC results demonstrate a strong relationship of MDD to substance dependence and a weak relationship to substance abuse. [11]

This finding is supported by genetic studies that have identified factors common to both MDD and alcohol dependence, and epidemiologic findings of excess MDD in former alcoholics.

The 2006 BRFSS found that those who drank alcohol heavily were significantly more likely than those who did not to have current depressive symptoms. [16]

27. DEPRESSION: ROLE OF PRIMARY CARE

Primary care is the front line for reducing the burden of depression.

Most patients with psychological problems seek help from their primary care doctor rather than a mental health specialist. [17-20]

The role of primary care providers is probably so vital because of patients’ ongoing relationship, and comfort level, with their primary care physicians, as well as the stigma associated with seeing a mental health specialist. [21,22]

Anxiety and depression are among the most common concerns seen in primary care. [18,23-25]

Depression is a common and debilitating illness. It is treatable, but the majority of people with depression do not receive even minimally adequate treatment. [26]

The USPSTF recommends routine depression screening for adult patients, if the practice has "systems in place to follow up with an accurate diagnosis, effective treatment, and careful follow-up. [27]

Considerable effort has gone into promoting screening and intervention for depression in primary care. This effort includes guidelines and recommendations, CME opportunities, tools and protocols to facilitate the process, and clinical trials that demonstrate efficacy. [6]

28. DEPRESSION: IMPACT ON HEALTH AND DISEASE

Major depressive disorder (MDD) is one of the most pressing public health problems in the United States. Depression is associated with substantial impairment, [29-31] co-morbidity, [29-31] poor health, [32] and mortality. [33]

Quality of LifePeople diagnosed with depression experience long-lasting problems in daily functioning and sense of well-being, comparable to or worse than patients with chronic illnesses such as diabetes or congestive heart failure. [6]

Depressed patients continue to suffer symptoms and depressive episodes even at 2 years of follow-up.

Causes suffering, decreases quality of life, and impairs social and occupational functioning. [34]

An evaluation of 17,558 outpatients of 181 PCPs in 7 managed care organizations found that depressed patients had significantly worse HRQOL than patients who have other chronic conditions. [35]

Overall, approximately 8 out of 10 people with moderate to severe depression reported some level of difficulty in functioning, and greater than 1 in 4 reported serious difficulties in work and home life because of their depressive symptoms. [7]

35% of males and 22% of females with depression reported that their depressive symptoms made it very or extremely difficult for them to work, get things done at home, or get along with other people.

More than half with mild depressive symptoms had some difficulty in daily functioning attributable to their symptoms.

DisabilityDepressive illness is projected to be the second leading cause of disability worldwide in 2020, next to ischemic cardiovascular disease. [36]

Persistently depressed people had 5 times greater functional disability compared with the non-depressed group over 3 years of follow-up. [37]

The MacArthur Study of Successful Aging showed that high depressive symptoms were associated with an increased risk of onset of disability in activities of daily living (ADL) for both men and women, the combination initiating a spiraling decline in physical and psychological health. [38]

There is a dose-response relationship between level of depression and incidence of angina (highest levels had twice the risk as lowest levels). [43]

Patients with a history of heart attacks have 1.8 times more depressive episodes in a year and more persistent symptoms than depressed patients without a history of heart attacks. [6]

High levels of depressive symptoms are associated with increased risks of MI and mortality over time. [44]

The relationship between depression and poorer heart failure outcomes is consistent and strong across multiple end points. [45]

Depressive symptoms during early adulthood are associated with higher levels of carotid intima-media thickness in men but not in women. [46]

DiabetesDepressive symptoms at baseline have been associated with higher follow-up blood glucose levels and an increased risk of developing Type 2 diabetes. [47]

Depressed adults have a 37% increased risk of developing type 2 diabetes mellitus, but the pathophysiological mechanisms underlying this relationship are still unclear. [48]

Individuals in the highest quartile of depressive symptoms had a 63% increased risk of developing diabetes compared with those in the lowest quartile. [49]

ObesityObesity in women has been related to episodes of major depression. [50]

ElderlyDepression is not considered a part of the normal aging process and is different than bereavement or grief. Depression in the elderly leads to decreased functional status and increased mortality. [11a]

Suicide in the elderly is also a concern. The primary risk factor for suicide and suicidal thoughts in the elderly is depression. [51a]

The elderly have the highest rates of suicide among all age groups. While the elderly comprise about l3% of the U.S. population, they account for approximately 20-25% of completed suicides. [11a,51a]

29. DEPRESSION: CURRENT PRACTICE PATTERNS

Identification: Primary care physicians are the providers most likely to see patients with depression.

Relatively few patients with depression see a mental health professional: [7]

1 in 7 with mild symptoms

Fewer than 1 in 4 with moderate symptoms

Fewer than 2 in 5 with severe depression

Despite the efforts to enhance depression screening, diagnosis and treatment in primary care, many clinicians still do not routinely assess and assist patients with symptoms of depression. [18-20,25,51,52]

Studies have shown that usual care by primary care physicians fail to recognize 30% to 50% of depressed patients. [25,53,54]

The 2005 National Survey on Drug Use and Health showed that at least 1 in 3 adults with a major depressive episode in the past year received no treatment for it. [55]

More men than women were untreated (44.4% vs 29.1%)

Blacks and Hispanics were less likely to be treated (43.6 and 49.8% not treated).

Up to one in four primary care patients suffer from depression; yet, primary care doctors identify only one-third (31 percent) of these patients. [56]

The accuracy of depression recognition by non-psychiatrist physicians without a standardized protocol is low. [57]

Treatment:Even when identified, evidence based treatment is under-used, especially in minority and older patients. [19,20,58,59]

Only 6 in 10 patients with major depressive disorder received treatment specifically for their depression in 2001and 2002. [11,15]

Mean age of treatment – 33.5 years, with a lag time of about 3 years between onset and treatment.

The NESARC indicated a continued lack of treatment for many respondents with major depression, especially in men where half received no treatment.

Only 46% to 57% are receiving treatment and only 18% to 25% are adequately treated. [31]

There are many reasons people with depression do not receive treatment. [60]

Some do not realize they have an illness that can be treated.

Some do not believe treatment works.

Other barriers to treatment include the stigma surrounding mental illness and mental health treatment and lack of insurance coverage for mental health care.

In community practice, only one third of patients treated for depression reached full remission after acute-phase treatment. [62]

30. DEPRESSION: SCREENING AND DIAGNOSIS

Screening Benefits from screening are unlikely to be realized without systems in place to ensure follow-up, as recommended by the USPSTF. [27,63]

Considerable evidence from randomized controlled trials (RCTs) shows that depression treatment (both medications and counseling) can be improved in primary care settings when it involves a systematic method to:

Provide care management with close follow-up by a non-physician working with the primary care physician

Enhance collaboration with mental health providers

Provide education and self-management support

There is no evidence that simple brief messages alone have any effect.

The key message is that systems need to be implemented in primary care to ensure proper follow-up of patients who screen positive for depression. This includes diagnostic procedures, treatment and management plans and ongoing follow-up.

Diagnosis and MonitoringThe Robert Wood Johnson Diabetes Initiative suggests that the PHQ-2 and PHQ-9 can readily be done in a variety of practice settings. [66]

The PHQ-2 was found to be very feasible for routine enrollment for group classes.

Asking the following two questions (PHQ-2) are as effective as longer screening instruments:

Over the past 2 weeks, have you ever felt down, depressed, or hopeless?

Over the past 2 weeks, have you felt little interest or pleasure in doing things?

In primary care, the patient health questionnaire (PHQ)-9, a nine-question survey, is a validated and reliable tool that the primary care physician can use to diagnose and treat depression and to monitor progress. [64,65]

A score of 10 or higher is used as the cutoff for a clinical diagnosis of depression and as an indication of the need to begin therapy.

A meta-analysis found a sensitivity of 0.77 and a specificity of 0.94.

The positive predictive value in an unselected primary care population was 59%, which increased to 85-90% when the prior probability increased to 30-40%.

The PHQ-9 should be assessed at every visit essentially as a lab test of depression severity/improvement. [66a]

A patient who expresses suicidal ideation and/or a plan needs further assessment (evaluation of suicide risk factors) and perhaps psychiatric referral on a non-urgent or urgent basis, depending on the circumstances.

Any positive or equivocal response should be followed up immediately with the following:

Ask about the specific nature of the ideation, intent, plans, and actions.

Develop a safe plan for further evaluation and treatment, which depending on the level of risk may range from continued primary follow-up alone to outpatient or emergency psychiatric evaluation.

A sensitivity to high-risk situations in depressed patients and clear documentation that suicidality was assessed in patients being treated for depression are appropriate in the primary care setting, and may uncover occasional patients who make their intent known and are amenable to intervention. [66c]

Overcoming Reluctance to Address SuicideClinicians worry at times that asking about suicide will initiate suicidal thoughts or actions, but there are no data to support this concern. [66c]

In contrast, many patients appreciate the opportunity to discuss suicidal thoughts, and may not verbalize these issues without being prompted. Sometimes the only clue to a suicidal patient is the initiation of an office visit.

Referral Although primary care clinicians capably manage more than 75% of patients with depression, referral for psychiatric evaluation is recommended in patients with the following: [67]

history of psychosis or suspected of having a primary psychotic disorder

potentially suicidal

history of bipolar disorder or symptoms of mania

substantial trouble tolerating medication adverse effects

depression that has not responded to 2 adequate trials of antidepressants

Guidelines for Approach to Managing Major Depression According to the APA practice guidelines, the specific components of managing patients with MDD include:

performing a diagnostic evaluation

evaluating the safety of the patient and others

evaluating the level of functional impairment

determining a treatment setting

establishing and maintaining a therapeutic alliance

monitoring the patient’s psychiatric status and safety

providing education to patients and families

enhancing treatment adherence

working with patients to address early signs of relapse [67a]

31. DEPRESSION: MANAGING DEPRESSION

Depression is a treatable condition. Effective treatments are available. [68,69]

Successful treatment enables people to return to the level of functioning they had before becoming depressed. [7]

The majority of people with depressive disorders improve when they receive appropriate treatment. [70]

The first step is a physical examination to rule out other possible causes of symptoms.

Next, a diagnostic evaluation for depression or referral to a mental health professional for evaluation.

Treatment choice depends on the diagnosis, severity of symptoms, and preference.

A variety of treatments, including medications and short-term psychotherapies (i.e., "talking" therapies), have proven effective for depression.

In general, severe depressive symptoms, particularly if recurrent, require a combination of treatments for the best outcome.

Once the patient is feeling better, treatment may need to be continued for several months-and in some cases, indefinitely-to prevent a relapse.

Follow-up is critical

Patients need to be monitored (by phone or visit) every one to two weeks for six to eight weeks during the initiation phase of new pharmacologic treatment. [70a]

The AHCPR Panel recommended that more severely depressed patients be seen at least twice a month for supportive care]. The PHQ-9 tool may be used to assess depression response over time. [70b]

Approach to Treatment The goal of the initial treatment phase is to achieve remission either by pharmacotherapy, psychotherapy, or a combination of modalities. [71]

Continuation and maintenance phases aim at preventing relapse and lifelong recurrence; the PHQ-2 or PHQ-9 score can guide clinicians on treatment modifications and the need for referrals for psychiatric evaluation.

Frequent follow-ups have been associated with better outcomes; 3 contacts within the 12 weeks after initial diagnosis are considered ideal.

Pharmacotherapy and psychological therapy are the cornerstone of treatment. [72]

Antidepressant medications for major depression, including tricyclic antidepressants (TCAs) and selective serotonin reuptake inhibitors (SSRIs), are clearly more effective than placebo.

Studies using "usual care" comparison groups in real-world settings have produced similar effects.

Second-generation antidepressants (SSRIs) dominate the management of depression, but do not substantially differ in efficacy or effectiveness from first generation drugs (TCAs).

Differences with respect to onset of action and adverse events may be relevant for the choice of a medication.

Psychosocial and psychotherapeutic interventions are probably as effective as antidepressant medications for major depression and more acceptable for many, but they are clearly more time-intensive and require referral or therapist training. [73]

The severity of depression must be considered. For severe levels of depression, pharmacotherapy may be necessary.

Combined psychotherapy and pharmacotherapy have been shown to be more efficacious than either alone. [75]

A lifestyle approach is another option; some people, especially milder cases, prefer this approach for the overall health benefits. [75a]

Managing the Elderly PatientAs in younger patients, depression in the elderly is treatable. [11a]

A meta-analysis of 89 controlled studies of treatments of depression in older patients found that both psychotherapy and pharmacotherapy work, with effect sizes that are moderate to large. [74]

Treatment choice should be based on other criteria, such as contraindications, treatment access, or patient preferences.

Pharmacologic therapy is often more challenging because of the presence of co-morbid conditions and/or other medications. [11a]

The current feeling is that SSRIs are first-line agents with serotonin norepinephrine reuptake inhibitors (SNRIs) such as venlafaxine or duloxetine as second line agents.

TCAs and monoamine oxidase inhibitors (MAOIs) are infrequently used anymore in treating elderly.

SSRIs tend to have fewer side effects, thus patients tend to tolerate them better.

SSRIs also have the advantage of being safer than TCAs in the event of an overdose.

Psychotherapy is also effective for treatment of depression in the elderly and the combination of drug therapy with psychotherapy can be quite helpful.

Managing Suicide RiskThe PRoSPECT trial showed that a combination of an SSRI (citalopram) and "depression care managers" led to resolution of suicidal ideation faster than "usual care." [51a]

The Importance of SupportA meta-analysis showed that interventions that included the spouse had positive effects on depression, in some cases, on mortality. [77]

Anti-Depressant Medications

Older anti-depressant therapy

An Agency for Healthcare Research Quality (AHRQ) review of 32 pharmaceutical and herbal treatments for depression found that older drugs (tricyclic anti-depressants or TCAs) are generally as efficacious as newer drugs (SSRIs). [6]

The study also found that patients discontinue their use of these drugs at similar rates (4-5%), although the two categories of drugs differ in the kinds of side effects patients are most likely to experience.

Serum levels for TCAs should be monitored if an inadequate response is obtained on a therapeutic dose. Some TCAs, such as nortriptyline, have a therapeutic window that needs to be achieved.

Second generation anti-depressants

An American College of Physicians (ACP) guideline and evidence review made 4 recommendations concerning the use of second-generation antidepressants for major depressive disorder: [78]

Modify treatment if the patient does not have an adequate response within 6 to 8 weeks of initiation of therapy (Grade: strong recommendation; moderate-quality evidence).

Continue treatment for 4 to 9 months after a satisfactory response with a first episode. For 2 or more episodes, an even longer duration of therapy may be beneficial (Grade: strong recommendation; moderate-quality evidence).

Current evidence does not warrant the choice of one second-generation antidepressant over another based on efficacy and effectiveness. [79]

However, the incidence of specific adverse events and the onset of action differed, so these are relevant in the choice of a medication.

A Cochrane review showed that the frequency of specific adverse events differs across drugs. [80]

Venlafaxine had a significantly higher rate of nausea and vomiting than selective serotonin reuptake inhibitors.

Paroxetine led to more sexual adverse effects and bupropion to fewer such effects;

Assessing Response to Anti-Depressant TherapyIt generally takes about 6-8 weeks to assess the maximal response to antidepressant therapy. A determination made before this time is open to question.

A meta-analysis of 50 RCTs found that about a third of the maximal therapeutic response is observed after the first week, but the maximal response may take 6 weeks or longer. [80a].

In the multicenter STAR*D trial, the mean time to achieve response was 5.7 weeks and the mean treatment time to remission was 6.7 weeks. [80b]

More than half of eventual responders to fluoxetine treatment began to respond by week 2; over 75% had begun to respond by week 4. [80c]

The lack of onset of response at 4-6 weeks was associated with a 73%-88% chance that patients would not respond.

If a patient is not responding by 8 to 12 weeks, it could mean that either the dose is inadequate or that particular antidepressant is not effective for the patient. Options include increasing to the maximum therapeutic dose, a trial of another antidepressant or referral to a psychiatrist [80d].

Anti-depressants in the ElderlyThe general prescribing rule of "start low, go slow" applies.

Elderly patients clear drugs more slowly, so it's advisable to start with a lower dose than the usual adult dose and gradually increase it to the therapeutic dose range.

As an example, the current prescribing information for Paxil CR (see www.paxil.com) recommends starting the drug at a reduced dosage in elderly patients since drug concentrations were notably higher in elderly patients compared to non-elderly.

As with any psychoactive drug, SSRIs have adverse effects of concern to the elderly including impairment of psychomotor skills and alterations in thought or judgment.

SSRIs have also been associated with movement disorders and, in the case of paroxetine, hyponatremia (low serum sodium concentration).

SSRIs(and other types of antidepressants have the potential for drug-drug interactions that must be taken into consideration before a particular medication is prescribed.

psychodynamic therapy, when complex early experiences are involved [75a]

Concerns over the clinical effectiveness of psychological therapies compared to usual general practitioner (GP) care or treatment with antidepressants were evaluated in a meta-analysis of 10 RCTs comparing psychological intervention with either usual GP care or antidepressant medication for major depression. [82]

The analysis showed greater effectiveness of psychological intervention over usual GP care in both the short term and long term.

There is renewed interest in behavioral therapy. A systematic review of 17 RCTs showed behavioral therapies to be superior to controls, brief psychotherapy, supportive therapy and equal to cognitive behavioral therapy. [83]

Behavioral therapy is an effective treatment for depression with outcomes equal to that of the current recommended psychological intervention.

The cost-effectiveness of psychological interventions has been questioned.

A meta-analysis showed that psychotherapy was more expensive than usual care, but not significantly more expensive than antidepressant treatment. [84]

There are indications that the cost-effectiveness of depression treatment on the whole may be improved by incorporating psychological treatments tailored to the needs of individual patients and/or providing them by trained nurses instead of psychologists or psychotherapists.

Preventing major depression in those with milder symptomsSub-threshold depression has a considerable impact on the quality of life and carries a high risk of developing major depressive disorder.

A meta-analysis of 7 high quality RCTs examining the effects of psychological treatments for sub-threshold depression found a relative risk of 0.7 for developing a major depressive disorder in subjects who received the intervention. [85]

They have potential to impact the entire range of associated medical and behavioral conditions and co-morbidities.

Many patients are interested in non-pharmacological approaches.

The strategies may reduce stigmatization.

However, they have not yet become a routine part of managing mood disorders in clinical practice. [87-90]

ExerciseMany studies have demonstrated the positive psychological effects of regular aerobic exercise in healthy people, including reduced perceived stress, reduced anxiety or depressive symptoms, and an increase in self-esteem. [87-89]

There is also solid evidence that regular exercise is associated with therapeutic effects in patients suffering from depressive and possibly other psychiatric disorders.

There is experimental evidence that regular exercise induces a downregulation of certain central serotonergic receptors, which play an important role in the pathogenesis of anxiety and depression. [95]

A Cochrane review reported that exercise seems to improve depressive symptoms in people with a diagnosis of depression, but the effect is only moderate, and not statistically significant when only the highest quality trials are included. [96]

Relaxation techniques were more effective at reducing symptoms than minimal treatment.

However, they were not as effective as psychological treatment.

Relaxation may be appropriate as a first-line treatment in a stepped care approach to managing depression, especially in younger populations and populations with sub-threshold or first episodes of depression. [97]

A decade ago, treatment leaders discouraged treating MDD in patients with substance dependence until the substance dependence was resolved.

Over time, epidemiologic surveys and clinical trials have changed the picture, so that treating both disorders simultaneously is common practice today.

Depression and substance abuse are common and costly disorders that frequently co-occur, but controversy about effective treatment for patients with both disorders persists. [99]

A systematic review to quantify the efficacy of antidepressant medications for treatment of combined depression and substance use disorders showed that antidepressant medication exerts a modest beneficial effect for patients with combined depressive- and substance-use disorders.

In this instance, medication should not be a stand-alone treatment, and concurrent therapy directly targeting the addiction is also indicated.

However, another systematic review of the efficacy of antidepressant drugs in patients with alcohol use disorders and co-morbid depression, was inconclusive regarding the effectiveness of antidepressants for alcohol dependence with co-morbid depression. [100]

32. DEPRESSION: ENHANCING PRIMARY CARE

Three aspects of depression care need to be addressed:

Many patients with depressive symptoms are not identified

When identified, treatment is often inadequate; brief advice is clearly not enough

Office systems are not set up to provide ongoing care; depression is not treated like a chronic episodic disease in which the care plan needs to respond to current needs

Improving outcomes for patients with major depression is not as simple as prescribing a new treatment: the whole process of care needs to be enhanced. [101,102] These enhancements include:

Changes in the organization and function of healthcare teams, like those used to improve outcomes in other chronic diseases [103]

Use of treatment guidelines, patient education, and screening procedures

Responsibility for active follow up taken on by a case manager (e.g., a practice nurse) by telephone

Adherence and outcomes monitored, treatment plans adjusted, and a relationship established with a mental health professional for consultation and referral when necessary [104,105]

A number of barriers have been identified that impede the delivery of effective care for people with depressive symptoms. [18,20,106,107] These include:

Time constraints

Reimbursement disincentives

A perceived lack of self efficacy to address emotional issues

Concerns about the risk of stigmatizing patients with the diagnosis and treatmen

The long-term care of patients with persisting depressive symptoms may be well served by adding a disease management component to the overall treatment strategy. [108]

The ultimate goal is remission, but it is often elusive.

Therapeutic strategies need to be adjusted for treatment resistant patients.

The STAR*D trial has shown the value of trying different psychopharmacological approaches, switching antidepressants or augmenting antidepressants that have induced partial remission. [108a]

Failure to achieve remission should be grounds for a specialty referral or at least consultation

Need to tailor treatment plan:Better matching of treatment plans to patient preferences, and potentially increased use of evidence-based options, should enhance satisfaction as well as outcomes. [18,109-112]

Categorizing depression as mild, moderate or severe will help develop appropriate management and therapeutic strategies. [113] An example of classification criteria from the VA/DoD guidelines: [113a]

Mild: minor symptoms (e.g., depressed mood, mild insomnia) OR some difficulty in social, occupational or school functioning, but functioning pretty well with some meaningful interpersonal relationships

For milder symptoms, the evidence is not so definitive for pharmacotherapy, thus patient preferences play a larger role. [113

Need to involve patients in care:Primary care patients suffering from major depression who are involved in decisions about their care and receive mental health treatment (antidepressants and/or therapy) are more satisfied with their care. [114]

In the Quality Improvement for Depression Study, less than half (43%) of patients received appropriate care for depression (26% received antidepressants, 28% counseling, and 10% both).

Primary care patients who received mental health care were 1.6 times more likely to be satisfied with their care than those who did not receive such care.

Patients who shared decision-making with their doctors were nearly three times more likely to be satisfied with their care than those who were not involved in decisions.

Collaborative Models:The collaborative care model appears to be the most effective for depression management in primary care and addresses system weaknesses, particularly those associated with follow-up care. [18,71,115-117]

It involves structured care relying more on non-medical specialists to augment primary care.

It seems well suited to the management of more complicated bio-psychological issues such as depression, which often also have associated co-morbidities.

Evidence supports the use of collaborative models, but little is known about which aspects of these complex interventions are essential. [118]

A systematic review of 37 RCTs that compared collaborative care with usual care in patients with depression showed that depression outcomes were improved at 6 months and evidence of longer-term benefit was found for up to 5 years.

Effect size was directly related to medication compliance and to the professional background and method of supervision of case managers.

The addition of brief psychotherapy did not substantially improve outcome, nor did increased numbers of sessions.

Predictors of favorable outcomes were shown in another review to be the systematic identification of patients, the professional background of staff (more training in mental health) and specialist supervision. [119]

Another systematic review found that adapted models of care, including quality improvement and collaborative care, are more effective than usual care in treating depression in racial and ethnic minority women. [120]

Although medication and psychotherapy were both effective in treating depression, low-income women generally needed case management to address related social issues.

Allowing patients to select the treatment of their choice (medication or psychotherapy or a combination) while providing outreach and other supportive services (case management, childcare and transportation) appear to result in optimal clinical benefits.

A systematic review of RCTs investigating the effectiveness of disease management programs (DMP) compared with usual primary care showed that DMP had a significantly better effect on depression severity. [121]

Patient satisfaction and adherence to the treatment regimen improved significantly.

DMP significantly enhance the quality of care for depression. Costs are within the range of other widely accepted public health improvements.

A systematic review of studies that investigated the effectiveness of using case management in the care of depression in primary health care found that case management improved management of major depression. [122] Case management:

Is more likely to achieve remission after 6-12 months [1.4 times the control group]

Promotes better medication adherence [1.5 times the control group]

Is more likely to achieve a clinical response [1.8 times control]

33. DEPRESSION: CHALLENGES

The challenges to improved depression care include:

Recognizing and treating a greater proportion of patients with depressive symptoms.

With a third to half of patients with depressive symptoms not receiving appropriate treatment, and with the negative impact on quality of life, substance abuse and the management of co-existing chronic disease – improved recognition and management is vital.

More individualized treatment plans, with greater consideration of patient preferences.

About 2 out of 3 patients with diagnosed depression fail to achieve remission. [123]

Incomplete remission is associated with increased risk of relapse, suicide, functional impairment, and higher use of health care resources.

Individual differences in therapeutic response contribute to inadequate treatment and are linked to numerous clinical and neurobiological factors, including noncompliance, underdosing, intolerance, disturbances in neural circuitry, and genetic variability in neurotransmitters.

Better understanding of motivational issues in counseling.

A systematic review showed that depressed patients are 3 times as likely to be noncompliant with medical treatment recommendations as non-depressed patients. [124]

Overcoming patients resistance to being diagnosed and treated.

Over half in a small qualitative study refused to accept the diagnosis. [125]

Contributing factors included:

fear of stigmatization and skepticism about the usefulness of labeling

feeling that depressive symptoms were a normal and transitory reaction to adversity

doubts about the necessity and effectiveness of treatment

These authors recommend soliciting the patient’s views on depression before diagnosing and offering treatment.

34. DEPRESSION: CLINICAL APPROACH: THE INITIAL CONSULT

The PHQ-2 is a validated and reliable depression screening tool for primary care. [71]

With a positive screening, the PHQ-9 is a validated and reliable tool to diagnose and treat depression and to monitor progress. [71]

A score of 10 or higher is the cutoff for a clinical diagnosis of depression and as an indication of the need to begin therapy.

However, a clear differential diagnosis that rules out other possible causes of the depressive symptoms, including bipolar disorder, psychosis, medical conditions, etc. must be carried out prior to initiating treatment.

Assessment of suicidal risk should be included. [71]

A positive score on the 9th item of PHQ-9 is a red flag for suicidal risk.

Assessment should include:

What is the nature of the suicidal ideation? Is there a plan?

Evaluate risk factors for suicide?

S – Sex: Males 3x as likely to commit suicide

A – Age: Older > younger

D – Depression: 70% have depression

P – Previous Attempts: Multiple attempts more likely to try again, however most deaths occur on first or second attempt

A contract for safety - in low-risk, may take the form of simply contracting with the primary care physician; in a higher-risk patient, the clinician may wish to involve a psychiatrist on an outpatient or more urgent basis

The goal of the initial treatment phase is to achieve remission either by pharmacotherapy, psychotherapy, or a combination of modalities.

Success in depression management largely depends on enabling patients to be active participants in their care. [71]

Clinicians can help by providing educational materials or directing patients to available resources.

They can remind patients that depression, like asthma or diabetes, is a chronic and recurring disorder, the management of which requires their participation.

They can educate patients regarding their medication, letting them know that 2 to 4 weeks of drug therapy may be needed before symptoms improve and alerting them to any potential adverse effects.

They can remind them of the importance of taking their medication daily, continuing their medication for at least 6 months after they are feeling better, and consulting their physician if adverse effects or other problems with medication occur or before changing the dosage of or discontinuing medication.

Patients should be advised of the importance of eating a healthy diet, avoiding alcohol, and obtaining enough sleep.

Improving Quality of Care for People With Depression. Translating Research Into Practice. Fact Sheet. AHRQ Publication No. 00-P020, January 2000. Agency for Healthcare Research and Quality, Rockville, MD. http://www.ahrq.gov/research/deprqoc.htm

Wells KB and Sherbourne CD. Functioning and utility for current health of patients with depression or chronic medical conditions in managed, primary care practices. Archives of General Psychiatry 1999; 56: 897-904.